Many stress-related mental illnesses, including depression and post-traumatic stress disorder (PTSD), occur at least twice as often in women as in men. While social and cultural factors certainly may contribute to this statistic, potential neurobiological reasons for this discrepancy have been inadequately investigated. Depression and PTSD are characterized by dysfunction of an area of the brain called the prefrontal cortex (PFC), which is known to govern higher cognitive abilities like concentration and short-term memory. These functions have been shown in lab animals to be disrupted after exposure to stress. However, the experiments have largely been done only in male animals, and sex differences in how the PFC responds to stress are unknown. A better understanding of such processes may help to elucidate the reason that women are more susceptible to stress-related disorders, and lead to the development of better anti-depressant treatments.

To examine the effects of stress on PFC function, male and female rats were exposed to different levels of mild stress, and then tested on a short-term memory task. The authors found that without stress, males and females performed equally well on the task. Likewise, after exposure to higher levels of stress, both males and females made significant memory errors. However, after exposure to a moderate level of stress, females were impaired, but males were not, suggesting that females were more sensitive to the PFC-impairing effects of stress. When the authors monitored the female rats' estrus cycles, they found that the rats showed this sensitivity only when they were in a high-estrogen phase. To further investigate the role of estrogen in this effect, Shansky et al removed the ovaries of a new group of female rats, thus eliminating any circulating estrogen. A time-release capsule containing either estrogen or placebo was implanted and the experiment repeated. Estrogen replacement had the same effect as natura
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Contact: Aimee Midei
molecularpsychiatry@mednet.ucla.edu
310-206-6739
Molecular Psychiatry
3-Dec-2003

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